MUCOSAL IMMUNOLOGY CORE PROJECT SUMMARY HIV is spread primarily via vaginal or rectal sexual transmission. In addition, the gut is a privileged site of HIV replication and a primary reservoir of virus that persists even during therapy with potent antiretroviral drugs. Furthermore, mucosal dysfunction during HIV infection is associated with morbidities and mortality. Considerable effort is now focused on novel therapeutic drugs, microbicides, and vaccines that can target the virus in the mucosal compartment. However, the tools, assays, and methods to access and study mucosal tissues and cells in non-human primates (NHP) are not yet adequate to meet the growing need to study this compartment. This project will develop resources required for the HIV research community to study the impact of antiretroviral drugs, microbicides, and vaccines on immune responses and the microbiota in different mucosal compartments in the NHP model. We also propose to develop a novel NHP specimen repository consisting of purified lymphocytes isolated from a wide range of tissues with an emphasis on mucosal tissues to support pilot studies and expand access to NHP samples in the research community without the need to purchase animals. Our specific aims will: 1) Optimize and refine methods and procedures to investigate mucosal immune responses in nonhuman primates, 2) establish a NHP specimen repository of lymphocytes isolated from various mucosal and systemic immune compartments in infected and uninfected nonhuman primates and 3) develop new resources that can be used to investigate the role of mucosal immunity and the microbiome in protection and pathogenesis in nonhuman primates. Together, these aims will establish new state-of-art resources and methods to investigate mucosal immunity and the microbiome in HIV disease, prevention and cure in nonhuman primates.